Effect of surfactant concentration on transdermal lidocaine delivery with linker microemulsions

A limited number of studies have been conducted to investigate the effect of surfactant concentration on microemulsion-mediated transdermal transport. Some studies suggest that increasing surfactant concentration reduces the partition of the active in the skin, and the overall transport. Other studies suggest that increasing surfactant concentration improves mass transport across membranes by increasing the number of “carriers” available for transport. To decouple these partition and mass transport effects, a three-compartment (donor, skin, receiver) mass balance model was introduced. The model has three permeation parameters, the skin-donor partition coefficient (Ksd), the donor-skin mass transfer coefficient (kds) and the skin-receiver mass transfer coefficient (ksr), also known as skin permeability. The model was used to fit the permeation profile of lidocaine formulated in oil-in-water (Type I) and water-in-oil (Type II) lecithin–linker microemulsions. The results show that surfactant concentration has a relatively minor effect on the mass transfer coefficients, suggesting that permeation enhancement via disruption of the structure of the skin is not a relevant mechanism in these lecithin–linker microemulsions. The most significant effect was the increase in the concentration of lidocaine in the skin with increasing surfactant concentration. For Type I systems such increase in lidocaine concentration in the skin was linked to the increase in lidocaine solubilization in the microemulsion with increasing surfactant concentration. For Type II systems, the increase in lidocaine concentration in the skin was linked to the increase in skin-donor partition. A surfactant-mediated absorption/permeation mechanism was proposed to explain the increase in lidocaine concentration in skin with increasing surfactant concentration. The penetration profiles of hydrophobic and amphiphilic fluorescence probes are consistent with the proposed mechanism.